{"doi":"10.1016/j.isci.2024.110591","title":"Dual effect of N-terminal deletion of cardiac myosin essential light chain in mitigating cardiomyopathy","abstract":"We investigated the role of the N-terminus (residues 1-43) of the myosin essential light chain (N-ELC) in regulating cardiac function in hypertrophic (HCM-A57G) and restrictive (RCM-E143K) cardiomyopathy mice. Both models were cross-genotyped with N-ELC-truncated Δ43 mice, and the offspring were studied using echocardiography and muscle contractile mechanics. In A57G×Δ43 mice, Δ43 expression improved heart function and reduced hypertrophy and fibrosis. No improvements were seen in E143K×Δ43 compared to RCM-E143K mice. HCM-mutant pathology involved an impaired N-ELC tension sensor, disrupted N-ELC-actin interactions, an altered force-pCa relationship, and a destabilized myosin's super-relaxed state. Removal of the malfunctioning N-ELC sensor led to functional rescue in HCM-truncated mutant hearts. However, the RCM mutation could not be rescued by N-ELC deletion, likely due to its proximity to the myosin motor domain, affecting lever-arm rigidity and myosin function. This study provides insights into the role of N-ELC in the development and potential rescue of ELC-mutant cardiomyopathy.","journal":"iScience","year":2024,"id":473721,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":354517,"name":"Katarzyna Kaźmierczak","orcid":"0000-0003-2153-2666","position":1,"is_corresponding":false},{"id":745518,"name":"Jingsheng Liang","orcid":null,"position":2,"is_corresponding":false},{"id":1310019,"name":"Andrew J. Kloehn","orcid":null,"position":3,"is_corresponding":false},{"id":1310020,"name":"Judith Vinod","orcid":null,"position":4,"is_corresponding":false},{"id":569760,"name":"Rosemeire M. Kanashiro‐Takeuchi","orcid":"0000-0002-7305-9172","position":5,"is_corresponding":false},{"id":354518,"name":"Danuta Szczesna‐Cordary","orcid":"0000-0002-8441-0722","position":6,"is_corresponding":false},{"id":744952,"name":"Yoel H. Sitbon","orcid":"0000-0001-6460-6421","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T02:06:04.967429Z","pmid":"39211545","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}